The Molecular Basis of 5α-Reductase Type 2 Deficiency

Abstract

The 5α-reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, playing a crucial role in male development. This enzyme is encoded by the <i>SRD5A2</i> gene, which maps to chromosome 2 (2p23), consists of 5 exons and 4 introns, and encodes a 254 amino acid protein. Disruptions in this gene are the molecular etiology of a subgroup of differences of sex development (DSD) in 46,XY patients. Affected individuals present a large range of external genitalia undervirilization, ranging from almost typically female external genitalia to predominantly typically male external genitalia with minimal undervirilization, including isolated micropenis. This is an updated review of the implication of the <i>SRD5A2</i> gene in 5α-reductase type 2 enzyme deficiency. For that, we identified 451 cases from 48 countries of this particular 46,XY DSD from the literature with reported variants in the <i>SRD5A2</i> gene. Herein, we present the <i>SRD5A2</i> mutational profile, the <i>SRD5A2</i> polymorphisms, and the functional studies related to <i>SRD5A2</i> variants to detail the molecular etiology of this condition.